We plan to use differentiating epithelial cells of rat small intestines as a model system for evaluating metabolic inhibitors which are potentially active against carcinoma of the colon. The advantages are that cell types which differ in mitotic rate and degree of specialization all have the same origin. They can be separated mechanically. Agents can be administered in vivo and results quantitatively evaluated in vitro. Expansion of system to colon would permit further comparison with cells in a tissue which has a high potential for malignant transformation. Ultimately, colons will be studied after administration of colonic carcinogens and tissues which can be tentatively viewed morphologically as pre-malignant will be examined. Current work has shown enzyme markers of the stages of cell maturation in the small bowel. Qualitative and quantitative changes in some of these enzymes have been seen following administration of inhibitors whose mode of action has been reasonably established in other systems. Those enzymes chosen for study are concerned with several regulatory systems. It is hoped that in addition to serving as a potential secondary screen, these studies could reveal bases for cellular specificities. Since enzymes of differentiation and division are regulated differently in colon and small bowel and since cancer of the colon is much more common, it appears reasonable that inhibitors might reveal sites of action by their pattern of effects on these enzymes. Further correlation in pre-malignant and malignant cells might permit prediction of potentially useful drugs.